The rod-shaped bacterium Myxococcus xanthus moves on surfaces along its long cell axis and reverses its moving direction regularly. Current models propose that the asymmetric localization of a Ras-like GTPase, MglA, to leading cell poles determines the moving direction of cells. However, cells are still motile in the mutants where MglA localizes symmetrically, suggesting the existence of additional regulators that control moving direction. In this study, we identified PlpA, a PilZ-like protein that regulates the direction of motility. PlpA and MglA localize into opposite asymmetric patterns. Deletion of the plpA gene abolishes the asymmetry of MglA localization, increases the frequency of cellular reversals and leads to severe defects in cell motility. By tracking the movements of single motor particles, we demonstrated that PlpA and MglA co-regulated the direction of gliding motility through direct interactions with the gliding motor. PlpA inhibits the reversal of individual gliding motors while MglA promotes motor reversal. By counteracting MglA near lagging cell poles, PlpA reinforces the polarity axis of MglA and thus stabilizes the direction of motility.

We have developed a novel, non-invasive nano-pulsed laser therapy (NPLT) system that combines the benefits of near-infrared laser light (808 nm) and ultrasound (optoacoustic) waves, which are generated with each short laser pulse within the tissue. We tested NPLT in a rat model of blast-induced neurotrauma (BINT) to determine whether transcranial application of NPLT provides neuroprotective effects. The laser pulses were applied on the intact rat head 1 h after injury using a specially developed fiber-optic system. Vestibulomotor function was assessed on post-injury days (PIDs) 1–3 on the beam balance and beam walking tasks. Cognitive function was assessed on PIDs 6–10 using a working memory Morris water maze (MWM) test. BDNF and caspase-3 messenger RNA (mRNA) expression was measured by quantitative real-time PCR (qRT-PCR) in laser-captured cortical neurons. Microglia activation and neuronal injury were assessed in brain sections by immunofluorescence using specific antibodies against CD68 and active caspase-3, respectively. In the vestibulomotor and cognitive (MWM) tests, NPLT-treated animals performed significantly better than the untreated blast group and similarly to sham animals. NPLT upregulated mRNA encoding BDNF and downregulated the pro-apoptotic protein caspase-3 in cortical neurons. Immunofluorescence demonstrated that NPLT inhibited microglia activation and reduced the number of cortical neurons expressing activated caspase-3. NPLT also increased expression of BDNF in the hippocampus and the number of proliferating progenitor cells in the dentate gyrus. Our data demonstrate a neuroprotective effect of NPLT and prompt further studies aimed to develop NPLT as a therapeutic intervention after traumatic brain injury (TBI).

The motility mechanism of certain rod-shaped bacteria has long been a mystery, since no external appendages (pili, flagella or cilia) are involved in their motion which is known as "gliding". The physical principles behind gliding motility still remain poorly understood. As a canonical example of such organisms, myxobacteria exhibit a gliding motility where the gliding speed depends on the substrate stiffness (1, 2): an effect known as mechanosensitivity. While there exist some physical models for the mechanosensitivity of eukaryotic cells in tissues due to adhesion (3), the mechanism of myxobacterial gliding motility remains unclear mainly due to the existence of a thin slime layer secreted between the cell and the substrate (4). Here we identify the physical principles behind gliding motility, and develop a theoretical model that predicts a two-regime behavior of the gliding speed as a function of the substrate stiffness. Our theory describes the elastic, viscous, and capillary interactions between the bacterial membrane carrying a traveling wave, the slime layer acting as a lubricating viscous film, and the substrate which we model as a soft solid. Defining the gliding motility as the horizontal translation under zero net force, we find the two-regime behavior is due to two different mechanisms of motility thrust. On stiff substrates, the gliding thrust arises from the elasto-hydrodynamic interactions between the bacteria, the slime and the substrate, whereby the bacterial shape deformations create a flow of slime exerting a pressure along the bacterial length. This pressure in conjunction with the bacteria shape provides the necessary thrust for propulsion. However, we show that such a mechanism cannot lead to gliding on very soft substrates. Instead, we show that including capillary effects along with the elasto-hydrodynamic interactions leads to formation of a ridge at the slime-substrate-air interface, which creates a thrust in the form of a localized pressure gradient at the tip of the bacteria. To test our theory, we performed experiments with isolated M. xanthus cells on agar substrates of varying stiffness. Over the whole range of substrate stiffness here investigated, the measured gliding speeds are found to be in good agreement with the predictions from our elasto-capillary-hydrodynamic model. The physical mechanisms of mechanosensitivity we propose serve as an important step towards an accurate theory of friction and substrate-mediated interaction between bacteria in a swarm of cells proliferating in soft media (5).Myxobacteria | gliding motility | mechanosensitivity | lubrication | elasto-capillary-hydrodynamics